基于cGAS-STING通路探讨知母皂苷元对脂多糖诱导的小鼠急性肺损伤保护作用

Protective effect of sarsasapogenin on LPS-induced acute lung injury in mice based on cGAS-STING signaling pathway

目的研究知母皂苷元对脂多糖(LPS)诱导的小鼠急性肺损伤的保护作用。方法将昆明小鼠随机分为对照组、模型组、地塞米松(0.5 mg/kg)组、知母皂苷元(50、100、200 mg/kg)组。知母皂苷元50、100、200 mg/kg组小鼠ig相应剂量知母皂苷元溶液,地塞米松组小鼠ip地塞米松磷酸钠注射液,对照组和模型组小鼠ig等体积生理盐水,1次/d,连续7 d。末次给药1 h后,其余各组小鼠除对照组外均ip 10 mg/kg LPS溶液复制小鼠急性肺损伤模型。6 h后取各组小鼠左肺组织,计算肺湿/干质量比(W/D);采用苏木精–伊红(HE)染色法观察肺组织病理形态学变化;采用酶联免疫吸附测定法(ELISA)检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平;采用Western blotting法检测肺组织中鸟苷酸–腺苷酸合成酶(c GAS)、干扰素基因刺激因子(STING)的蛋白表达。结果与模型组相比,知母皂苷元组小鼠左肺W/D值、血清中IL-6和TNF-α水平、肺组织中c GAS和STING的蛋白表达均显著降低(P<0.05),肺组织病理学损伤均有所改善。结论知母皂苷元可能通过抑制c GAS-STING通路,减少炎症因子TNF-α、IL-6的分泌,从而保护LPS诱导的急性肺损伤。

Objective To study the protective effect of sarsasapogenin on LPS-induced acute lung injury in mice.Methods KM mice were randomly divided into control group,model group,dexamethasone(0.5 mg/kg)group,and sarsasapogenin(50,100,200 mg/kg)group.Mice in the 50,100,and 200 mg/kg group were ig administered with the corresponding dose of the sarsasapogenin solution,the mice in the dexamethasone group were ig administered with Dexamethasone Sodium Phosphate Injection,and the control group and model group were ig administered with equal volume of normal saline once daily for 7 d.Afer the last administration of 1 h,mice in the other groups except the control group were treated with 10 mg/kg LPS solution to replicate the acute lung injury model of mice.After 6 h,the left lung tissues of each group were collected and the lung wet/dry mass ratio(W/D)was calculated.HE staining was used to observe the pathological changes of lung tissue.The serum levels of TNF-αand IL-6 were detected by ELISA.Western blotting method was used to detect the protein expressions of cGAS and STING in lung tissue.Results Compared with model group,the left lung W/D ratio,serum IL-6 and TNF-αlevels,and the protein expressions of cGAS and STING in lung tissue were significantly decreased(P<0.05),and the lung histopathological injuries were improved.Conclusion Sarsasapogenin may protect LPS-induced acute lung injury by inhibiting the cGAS-STING pathway and then reducing the secretion of inflammatory factors TNF-α.and IL-6.